Stimulating Cervical Neurons Sustains Post-Trauma Breathing

Michael’s Hospital (Toronto, Canada), and the Krembil Research Institute (Toronto, Canada), using a combination of pharmacogenetics and physiology assays in different models of SCI, found that mid-cervical excitatory interneurons--which form synapses on the phrenic motor neurons that control the main inspiratory muscle--can modulate phrenic motor output and diaphragmatic function.

Although these interneurons are not necessary for breathing under normal conditions, their stimulation in non-injured animals enhances inspiratory amplitude. But in a murine model, the researchers found that the same cells where crucial for promoting respiratory recovery after traumatic SCI, and that their stimulation restores respiratory motor function. The researchers suggest that targeting this latent cell subpopulation could provide a strategy to restore breathing after central nervous system (CNS) trauma. The study was published on October 10, 2018, in Nature.

“The big takeaway here is the identification of this novel neural circuit. We found is if we activate this population of neurons using pharmacogenetics, we can rescue breathing,” said senior author professor Michael Fehlings, MD, PhD, of the UT department of surgery. “The biggest implication of this work is that one day, we may be able to flip a switch and improve the breathing of people living with these injuries.”

Respiratory dysfunction is a major cause of morbidity and mortality during and following SCI, often necessitating a tracheostomy or long-term use of an assistive ventilation device. The trauma causes impairment of respiratory muscles, reduced vital capacity, ineffective cough, reduction in lung and chest wall compliance, and distortion of the respiratory system. Severely affected individuals may require assisted ventilation, which can also cause problems with speech production.

Related Links:
University of Toronto
St. Michael’s Hospital
Krembil Research Institute